Bioequivalence Study of CRushed TriUMeq With or Without Drip Feed Compared to the Whole Tablet

NCT02569346 | Completed Phase 1

• 1 other identifier: UMCN-AKF 15.02
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Dolutegravir is an HIV-1 integrase inhibitor which is marketed as a single tablet (Tivicay®) and in a fixed dose combination tablet with abacavir and lamivudine (Triumeq®, referred to as TRI). For patients with swallowing difficulties, administration of whole tablets can be problematic and tablets are cut or crushed to ease administration. Currently there is no information about crushing TRI tablets. Therefore this study will be conducted to investigate whether crushed and suspended TRI and crushed and suspended TRI with drip feed are bioequivalent to taking TRI as a whole.

Conditions

HIV

Keywords

Triumeq; Pharmacokinetics; Crushing; Drip feed

Outcome Measures

Primary Outcomes (1)

• AUC

  up to 48 hours after administration

Secondary Outcomes (1)

• Adverse events

  during the entire conduct of the study, 6 weeks in total

Study Arms (3)

Triumeq whole

ACTIVE COMPARATOR

Single-dose Triumeq as a whole tablet in a fasted state

Drug: Triumeq crushed + breakfast; Drug: Triumeq crushed + drip feed

Triumeq crushed + breakfast

EXPERIMENTAL

Single-dose crushed and suspended Triumeq in a fasted state

Drug: Triumeq; Drug: Triumeq crushed + drip feed

Triumeq crushed + drip feed

EXPERIMENTAL

250 ml drip feed (Nutrison) followed by a single-dose crushed and suspended Triumeq

Drug: Triumeq; Drug: Triumeq crushed + breakfast

Interventions

Triumeq DRUG

Single-dose Triumeq as a whole tablet

Triumeq crushed + breakfast; Triumeq crushed + drip feed

Triumeq crushed + breakfast DRUG

Single-dose crushed and suspended tablet of Triumeq

Triumeq crushed + drip feed; Triumeq whole

Triumeq crushed + drip feed DRUG

Drip feed followed by single-dose crushed and suspended tablet of Triumeq

Triumeq crushed + breakfast; Triumeq whole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is at least 18 and not older than 55 years of age at the day of screening.
• Subject weighs at least 40 kg.
• Subject has a BMI of 18.5-30 kg/m2, extremes included.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within four weeks prior to day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the Investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
• Subject has a normal blood pressure and pulse rate, according to the Investigator's judgment.
• Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to day 1.

You may not qualify if:

• Positive HIV test.
• Positive hepatitis B or C test.
• Positive HLA-B\*5701 status (the risk for abacavir hypersensitivity reaction to occur is high for subjects who test positive for the HLA-B\*5701 allele).
• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• Inability to understand the nature and extent of the study and the procedures required.
• Pregnant female (as confirmed by an hCG test performed less than 4 weeks before day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the study.
• Therapy with any drug (including herbal remedies, multivitamins, magnesium- and calcium-containing supplements, etc.) (for two weeks preceding day 1), except for acetaminophen.
• Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal disorders (renal failure determined as an estimated Glomerular Filtration Rate (eGFR) below 50 ml/min (MDRD-based)), hepatic disorders (Child-Pugh B or C), hormonal disorders (especially diabetes mellitus), coagulation disorders.
• History of or current abuse of drugs, alcohol or solvents.
• Gluten free diet.
• Participation in a drug study within 60 days prior to day 1.
• Donation of blood within 60 days prior to day 1.
• Febrile illness within 3 days before day 1.
• Co-worker of Radboud university medical center.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

CRCN, Radboud University Medical Center

Nijmegen, Netherlands

Location

Related Publications (1)

• Roskam-Kwint M, Bollen P, Colbers A, Duisenberg-van Essenberg M, Harbers V, Burger D. Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. J Antimicrob Chemother. 2018 Sep 1;73(9):2430-2434. doi: 10.1093/jac/dky191.

  PMID: 29796595 RESULT

MeSH Terms

Conditions

Pressure Ulcer

Interventions

abacavir, dolutegravir, and lamivudine drug combination; Breakfast

Condition Hierarchy (Ancestors)

Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Meals; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 6, 2015
• Study Start: March 1, 2016
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: December 7, 2020

Record last verified: 2020-12

Locations

NL (1)